Lynch Syndrome and Liver Disease - Connecting the Dots

Document Type

Conference Proceeding

Publication Date

10-1-2024

Publication Title

Am J Gastroenterol

Abstract

Introduction: Lynch syndrome (LS) is an autosomal-dominant disorder that increases risk of carcinogenesis via defects in DNA mismatch repair genes. Typically, it has been associated with colorectal and gynecological cancers, but has been more rarely been connected to biliary cancers as well. The intricate relationship between LS and liver disease is highlighted by the increased incidence of hepatobiliary manifestations, making vigilant screening and management imperative. Case Description/Methods: We report the case of an elderly White woman with hypothyroidism, who presented with a long history of persistently elevated Alkaline phosphatase, with presenting values of ALT 24, AST 30, ALP 305, and total bilirubin 0.50. She was asymptomatic without toxometabolic risk factors. The patient has an interesting family history of 2 sisters with PMS2 positive LS, one of whom also had autoimmune hepatitis (AIH) and intrahepatic cholangiocarcinoma, and a brother who underwent liver transplantation for cirrhosis of unknown etiology. Serologies positive for antimitochondrial antibody (AMA) of 17 U/mL, antinuclear antibody (ANA) ratio >1:55, SSA/SSB antibodies >240 and 167 U/mL, and positive smooth muscle antibody (SMA). Liver biopsy showed chronic cholestasis and patchy portal inflammation without bile duct inflammation or granulomas. She was initiated on Ursodiol and MRCP was ordered, with repeat bloodwork after 2 months showing near normalization of ALP to 144. Discussion: This case observes an elderly women with newly diagnosed PBC without cirrhosis, who prompted extensive hepatobiliary workup due to personal and family history of LS and liver disease. Mutations in PMS2 genes carry a lower risk for malignancy compared to other mismatch repair genes, which has led some experts to suggest less rigorous screening approach. However, as this case highlights, assessing for hepatobiliary manifestations of LS is extremely important. This case also demonstrates the importance of both laboratory and pathologic screening for various pathologies in liver disease. While family history, serologies and clinical presentation suggested LS and PBC, biopsy introduced new suspicion for PSC. Family history of idiopathic cirrhosis and cholangiocarcinoma further complicates the clinical picture, raising questions about the interplay between autoimmune liver disease and LS. This case advocates for a comprehensive and thorough evaluation for liver disease in patients with history of Lynch Syndrome.

Volume

119

Issue

10

First Page

S2885

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